We propose to develop an enzyme-linked immunoassay (ELISA) and a radioimmunoassay (RIA) capable of detecting antibodies to M. leprae specific protein antigen(s) to be used in an immuno-epidemiological study of leprosy in the countries of Sri Lanka (Proposal II) and Mexico (Proposal I). Antibody levels and skin test results will be obtained from untreated contacts of leprosy patients. This information will be correlated with subsequent development of tuberculoid leprosy (T) or lepromatous leprosy (L) in contacts with frequent or less frequent exposure to leprosy patients. Experiments will be performed to learn more about purification of leprosy bacilli from host tissues without the use of proteolytic enzymes. We will concentrate on protein antigens on the surface of M. leprae since we have obtained evidence outlined below that an antigen(s) exists that is relatively specific for M. leprae and that it is a protein located on the surface of M. leprae. This protein will be purified to a single component as evaluated by SDS polyacrylamide gel electrophoresis and its molecular weight and isoelectric point will be determined. It will then be used in a quantitative immunoassay to detect specific antibodies to this protein in sera from leprosy patients or contacts with leprosy patients. Antigen fractionation and purification will be performed both in Mexico and Seattle, and use of the purified M. leprae specific protein in a quantitative Enzyme Linked Immuno Sorbant Assay (ELISA) will be performed in all three countries. Personnel from the University of Washington will spend 5-6 months per year in each country to assist the development of the ELISA method and its application for testing sera contacts of leprosy patients. Separate funding will be sought to allow 2-6 month training periods for one collaborator each year either from Mexico or Sri Lanka to learn new immunochemical techniques in the Seattle laboratory.